RNA in Extracellular Vesicles

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: closed (25 November 2024) | Viewed by 5003

Special Issue Editors


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Guest Editor
Disease Networks Research Unit, Laboratory of Developmental Biology, Faculty of Biochemistry and Molecular Medicine, University of Oulu, 90570 Oulu, Finland
Interests: extracellular vesicles; extracellular RNA; astrocyte-derived extracellular vesicles; ncRNA; miRNA; mRNA; human sweat nucleic acids; metagenomics

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Guest Editor
HiPrep and EV Core, Institute for Molecular Medicine Finland FIMM, University of Helsinki, 00290 Helsinki, Finland
Interests: extracellular vesicles; transcriptomics; RNA; mRNA; small RNA; liquid biopsies; kidney disease; diabetes; cancer

Special Issue Information

Dear Colleagues,

RNA is secreted from living and dying cells by specialized membrane-bound organelles: the Extracellular Vesicles (EVs). RNA is also secreted in other ways, and is typically carried by particles that include other molecules such as proteins and lipids. RNA is an attractive analyte for liquid biopsy, but it is also a dynamic intercellular or interkingdom messenger. The transferred RNA of EVs or EPs (extracellular particles) can act as a gene expression modulator, and thus its therapeutic applications are under investigation. Consequently, the extracellular RNA research field is progressing at a rapid pace with regular twists and turns due to technical advances and challenges. Why is RNA secreted in EVs vs EPs? Are they signaling complexes destined for other cells or organisms, or just waste? What is their value for diagnostics or therapeutics? How do they function in complex host–microbiota or host–parasite systems, or in inter-organ communications in complex multicellular organisms?

The purpose of this Special Issue is to present original research or review articles that explore the various extracellular RNA types carried by EV or other nanoparticles from flora, fauna, fungi or bacteria in health and disease, as well as the mechanisms that regulate this secretion. We welcome articles from single miRNA biomarker studies using PCR to whole-transcriptome investigations via next-generation sequencing, the in silico analysis of sequences targeting RNA for secretion, and innovative multi-omics approaches for the characterization of RNA carriers and their interactive environment.

Dr. Genevieve Bart
Dr. Maija Puhka
Guest Editors

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Keywords

  • EV associated RNA
  • EV encapsulated RNA
  • novel RNA
  • regulatory RNA
  • ncRNA
  • mRNA
  • small RNA
  • miRNA
  • transcriptomics
  • PCR

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Published Papers (2 papers)

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Research

40 pages, 7779 KiB  
Article
Capturing the Kidney Transcriptome by Urinary Extracellular Vesicles—From Pre-Analytical Obstacles to Biomarker Research
by Karina Barreiro, Om Prakash Dwivedi, Antti Rannikko, Harry Holthöfer, Tiinamaija Tuomi, Per-Henrik Groop and Maija Puhka
Genes 2023, 14(7), 1415; https://doi.org/10.3390/genes14071415 - 8 Jul 2023
Cited by 3 | Viewed by 2232
Abstract
Urinary extracellular vesicles (uEV) hold non-invasive RNA biomarkers for genitourinary tract diseases. However, missing knowledge about reference genes and effects of preanalytical choices hinder biomarker studies. We aimed to assess how preanalytical variables (urine storage temperature, isolation workflow) affect diabetic kidney disease (DKD)—linked [...] Read more.
Urinary extracellular vesicles (uEV) hold non-invasive RNA biomarkers for genitourinary tract diseases. However, missing knowledge about reference genes and effects of preanalytical choices hinder biomarker studies. We aimed to assess how preanalytical variables (urine storage temperature, isolation workflow) affect diabetic kidney disease (DKD)—linked miRNAs or kidney—linked miRNAs and mRNAs (kidney-RNAs) in uEV isolates and to discover stable reference mRNAs across diverse uEV datasets. We studied nine raw and normalized sequencing datasets including healthy controls and individuals with prostate cancer or type 1 diabetes with or without albuminuria. We focused on kidney-RNAs reviewing literature for DKD-linked miRNAs from kidney tissue, cell culture and uEV/urine experiments. RNAs were analyzed by expression heatmaps, hierarchical clustering and selecting stable mRNAs with normalized counts (>200) and minimal coefficient of variation. Kidney-RNAs were decreased after urine storage at −20 °C vs. −80 °C. Isolation workflows captured kidney-RNAs with different efficiencies. Ultracentrifugation captured DKD -linked miRNAs that separated healthy and diabetic macroalbuminuria groups. Eleven mRNAs were stably expressed across the datasets. Hence, pre-analytical choices had variable effects on kidney-RNAs—analyzing kidney-RNAs complemented global correlation, which could fade differences in some relevant RNAs. Replicating prior DKD-marker results and discovery of candidate reference mRNAs encourages further uEV biomarker studies. Full article
(This article belongs to the Special Issue RNA in Extracellular Vesicles)
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49 pages, 10581 KiB  
Article
Human Adult Astrocyte Extracellular Vesicle Transcriptomics Study Identifies Specific RNAs Which Are Preferentially Secreted as EV Luminal Cargo
by Keerthanaa Balasubramanian Shanthi, Daniel Fischer, Abhishek Sharma, Antti Kiviniemi, Mika Kaakinen, Seppo J. Vainio and Geneviève Bart
Genes 2023, 14(4), 853; https://doi.org/10.3390/genes14040853 - 31 Mar 2023
Cited by 2 | Viewed by 2581
Abstract
Astrocytes are central nervous system (CNS)-restricted glial cells involved in synaptic function and CNS blood flow regulation. Astrocyte extracellular vesicles (EVs) participate in neuronal regulation. EVs carry RNAs, either surface-bound or luminal, which can be transferred to recipient cells. We characterized the secreted [...] Read more.
Astrocytes are central nervous system (CNS)-restricted glial cells involved in synaptic function and CNS blood flow regulation. Astrocyte extracellular vesicles (EVs) participate in neuronal regulation. EVs carry RNAs, either surface-bound or luminal, which can be transferred to recipient cells. We characterized the secreted EVs and RNA cargo of human astrocytes derived from an adult brain. EVs were isolated by serial centrifugation and characterized with nanoparticle tracking analysis (NTA), Exoview, and immuno-transmission electron microscopy (TEM). RNA from cells, EVs, and proteinase K/RNase-treated EVs was analyzed by miRNA-seq. Human adult astrocyte EVs ranged in sizes from 50 to 200 nm, with CD81 as the main tetraspanin marker and larger EVs positive for integrin β1. Comparison of the RNA between the cells and EVs identified RNA preferentially secreted in the EVs. In the case of miRNAs, enrichment analysis of their mRNA targets indicates that they are good candidates for mediating EV effects on recipient cells. The most abundant cellular miRNAs were also abundant in EVs, and the majority of their mRNA targets were found to be downregulated in mRNA-seq data, but the enrichment analysis lacked neuronal specificity. Proteinase K/RNase treatment of EV-enriched preparations identified RNAs secreted independently of EVs. Comparing the distribution of cellular and secreted RNA identifies the RNAs involved in intercellular communication via EVs. Full article
(This article belongs to the Special Issue RNA in Extracellular Vesicles)
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